ORLANDO—Statin therapy reduces the risk of a first major cardiovascular (CV) event in patients with type 2 diabetes and unremarkable cholesterol levels, said Helen Colhoun, MD, at the 64th Scientific Sessions of the American Diabetes Association (ADA).This finding strongly suggests that all patients with type 2 diabetes be treated with a statin, regardless of their cholesterol level.
She reported the findings from a study known as the Collaborative Atorvastatin Diabetes Study (CARDS), which is the first study of a lipid-modifying agent for the primary prevention of CV disease conducted solely in patients with type 2 diabetes. The study included 2838 patients with type 2 diabetes and low-density lipoprotein (LDL) cholesterol levels of =160 mg/dL who had no clinical history of coronary, cerebrovascular, or severe peripheral vascular disease. They were randomized to atorvastatin 10 mg/day or placebo. To be eligible, patients had to have one of the following CV risk factors in addition to diabetes: hypertension, retinopathy, micro- or macroalbuminuria, or currently smoking.
"Two thirds of the patients enrolled had LDL cholesterol levels below the current ADA guideline for pharmacologic intervention," said Dr Colhoun, coprincipal investigator of CARDS and professor of genetics and epidemiology, The Conway Institute, University College Dublin, Ireland. Twenty-five percent had an entry LDL cholesterol level of <100 mg/dL, which is the current target of therapy in patients with type 2 diabetes.
LDL cholesterol was reduced by 40% in the group assigned to atorvastatin compared with the group randomized to placebo. By 48 months, about 80% of the atorvastatin group reached their LDL cholesterol level treatment target of <100 mg/dL, compared with slightly more than 20% of the placebo group.
The trial was stopped 2 years before the planned termination date because of a significant benefit on outcomes associated with atorvastatin, she said. After approximately 4 years, atorvastatin recipients had a 37% reduction in the risk of major CV events ( = .001), including a 36% reduction in the risk of acute coronary events and a 48% reduction in the risk of stroke. The treatment effect was apparent regardless of baseline LDL cholesterol levels, baseline high-density lipoprotein cholesterol levels, and baseline triglyceride levels.
The number of events avoided per 1000 patients treated for 4 years was 36.7, and the number needed to treat for 4 years to prevent one event was 27.
The incidence of muscle- and liver-related adverse events was similar in the placebo and atorvastatin groups. Elevations of alanine transaminase more than 3 times the upper limit of normal occurred in 14 placebo recipients and 17 atorvastatin recipients; elevations of aspartate transaminase occurred in 4 and 6 patients in the 2 groups, respectively. No patient in either group had rhabdomyolysis.
Based on the results of CARDS, all patients with type 2 diabetes should be considered for statin therapy, regardless of their cholesterol level, said Dr Colhoun. "CARDS suggests that there is no justification for having a threshold level of LDL cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statin treatment," she said. "The overall cardiovascular risk should be the principal determinant."